This invention relates to novel nitrosourea derivatives which exhibit a high level of inhibitory activity against leukemia and tumors, to a process for the preparation thereof and to their use for pharmaceutical purposes.
There are a variety of compounds which have been proposed as being effective for inhibiting leukemia and tumors, one class of which is nitrosourea derivatives. Among the nitrosourea derivatives, streptozotocin [N-(N'-methyl-N'-nitrosocarbamoyl)-D-glucosamine] and its derivatives such as methyl glucosaminides are typical ones early developed (refer to U.S. Pat. No. 3,577,406 and U.S. Pat. No. 3,767,640, for example), but they are not satisfactory yet because of insufficient activity against leukemia and tumors and/or of undesirable side effects thereof. Another class of nitrosourea derivatives is a series of glycosyl derivatives of nitrosoureas which I have recently proposed, among which the most interesting compound is 1-(2-chloroethyl)-3-(.beta.-D-glucopyranosyl)-1-nitrosourea (abbreviated as GANU) which has a broad spectrum of antitumor activity against a wide variety of experimental leukemia and tumors with positive expectation of the efficacy in human cancer chemotherapy (refer to T. Suami et al., U.S. Pat. No. 4,086,415, U.S. Pat. No. 4,157,439 and U.S. Pat. No. 4,220,643). A further class of nitrosourea derivatives I have already proposed is 1-(2-chloroethyl)-3-(mono- or poly-hydroxy-substituted cyclohexyl)-1-nitrosoureas, of which the most preferred one is 1-(2-chloroethyl)-3-(1,3/2N-dihydroxycyclohexyl)-1-nitrosourea (abbreviated as DONU) which also has a broad spectrum of antitumor activity against a wide variety of experimental leukemia and tumors with a very low toxicity (refer to T. Suami et al., U.S. Pat. No. 4,180,655).